NEUROPROTECTION BY BOTH NMDA AND NON-NMDA RECEPTOR ANTAGONISTS IN IN-VITRO ISCHEMIA

We have investigated the relative contributions of oxygen and glucose deprivation to ischaemic neurodegeneration in organotypic hippocampal slice cultures. Cultures prepared from 10-day-old rats were maintained in vitro for 14 days and then deprived of either oxygen (hypoxia), gl ucose (hypoglycaemia), or both oxygen and glucose (ischaemia). Hypoxia alone induced degeneration selectively in CA1 pyramidal cells and thi s was greatly potentiated if glucose was removed from the medium. We h ave also characterised the effects of both pre- and post-treatment usi ng glutamate receptor antagonists and the sodium channel blocker tetro dotoxin (TTX). Neuronal death following either hypoxia or ischaemia wa s prevented by pre-incubation with CNQX, MK-801 or tetrodotoxin. MK-80 1 or CNQX also prevented death induced by either hypoxia or ischaemia if added immediately post-insult, however, post-insult addition of TTX prevented hypoxic but not ischaemic damage. Organotypic hippocampal s lice cultures are sensitive to both NMDA and non-NMDA glutamate recept or blockade and thus represent a useful in vitro system for the study of ischaemic neurodegeneration paralleling results reported using in v ivo models of ischaemia.